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Optimization of antibacterial properties of polymer-phosphate bone fillers
Grézlová, Veronika ; Michlovská, Lenka (referee) ; Vojtová, Lucy (advisor)
Tato diplomová práce je zaměřená na přípravu polymer-fosfátových kostních cementů. Cílem je optimalizovat antibakteriální vlastnosti daného cementu přídavkem selenových nanočástic (SeNPs). V teoretické části práce je popsána charakteristika kosti, vlastnosti fosforečnanu vápenatého (TCP) a jeho polymorfů, použití kostního cementu a antibakteriálních nanočástic v medicíně. Experimentální část se věnuje přípravě vzorků, popisu metod a vyhodnocení vlivu SeNPs na vytvrzování kostního cementu, morfologii, krystalinitu, mechanické, reologické a antibakteriální vlastnosti. Výsledkem je zvýšení injektovatelnosti cementu a zrychlení jeho vytvrzování včetně pozitivního vlivu na mechanické vlastnosti. Antibakteriální vlastnosti vzorků byly testovány použitím diskové i diluční metody, což vedlo k pozitivnímu inhibičnímu účinku SeNP na grampozitivních bakteriích (G+), zejména Staphylococcus aureus a methicillin rezistentní Staphylococcus aureus. Kvantitativní uvolňování SeNP z modifikovaného kostního polymer-fosfátového cementu umožňuje jeho použití jako antibakteriální kostní výplně (například pro léčbu zánětu kostí).
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Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity I
Brányik, Michal ; Zitko, Jan (advisor) ; Demuth, Jiří (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Title of the thesis: Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity I Author: Michal Brányik Supervisor: doc. PharmDr. Jan Zitko, Ph.D. Consultant: PharmDr. Martin Juhás, Ph.D. Antimicrobial resistance is an ever-growing problem that occurs worldwide. Many bacterial strains develop the ability to resist the otherwise efficient substances, thus posing a serious threat for the future. Mycobacterium tuberculosis (Mtb), the source of tuberculosis, is no exception. Given that it is the leading cause of death due to a single pathogen, many efforts have been put into finding new active compounds. The substances synthesized as a part of this thesis are based on previously prepared substances with potential antimicrobial activity. The basic structure consists of 2-aminooxazole or 2-aminothiazole and substituted pyridine or pyrazine carboxamides. The structures were confirmed by the 1 H and 13 C NMR spectra, IR spectra and mass spectrometry. All the substances were tested for in vitro activity against eight bacterial strains (four gram-positive and four gram-negative) as well as eight fungal strains (four yeast and four fungi). We also...
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Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity VI
Abdalrahman, Nechirwan Taimur ; Zitko, Jan (advisor) ; Nováková, Veronika (referee)
(In English) Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Nechirwan Abdalrahman Supervisor: Assoc. Prof. PharmDr. Jan Zitko, Ph.D. Title: Design, synthesis, and evaluation of heterocyclic compounds with potential antimicrobial activity VI Despite the existence of a well-established treatment regimens, tuberculosis (TB) continues to be the most leading cause of death by a single microorganism, as reported by WHO. One of the reasons behind treatment failure in completely eradicating this infection is drug resistance. Novel 3-(phenylureido)pyrazine-2-carboxamide derivatives, refer to figure below, were synthesized by reacting 3-chloropyrazine-2-carboxamide with ammonia to produce 3- aminopyrazine-2-carboxamide as an intermediate building block, followed by reacting with various substituted phenyl isocyanates using a microwave reactor. The synthesized compounds were evaluated for in vitro activity against various mycobacterial strains, where most active ones among them showed moderate to low activities; 4-tertiary butyl (MIC 62.5 µg/mL), 4-NO2 (MIC 62.5 µg/mL), 4-Bromo (MIC 250 µg/mL), 4-Cl (MIC 250 µg/mL), 2-F (MIC 250 µg/mL), and non-substituted (MIC 500 µg/mL). As a complementary study in silico, the synthesized...
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Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity IV
Fekri, Amir Hossein ; Zitko, Jan (advisor) ; Miletín, Miroslav (referee)
(English) Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Thesis title: Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity IV Candidate: Amirhossein Fekri Supervisor: doc. PharmDr. Jan Zitko, Ph.D. Consultant: Mgr. Vinod S. K. Pallabothula Tuberculosis has remained one of the deadliest infectious diseases worldwide caused by a single infectious agent, the rapid growth of resistance to anti-tubercular drugs hinders the successful control and treatment of TB worldwide, which challenges the scientific community to develop new drugs to improve currently available treatment. This diploma thesis represents the design, synthesis, and biological evaluation of two series of compounds including cyclized (pyrazine- oxazinone) and carboxamide derivatives as potentially active antimycobacterial agents sharing a pyrazine core as common structural features that could potentially target mycobacterial aspartate decarboxylase (PanD) and prolyl-tRNA synthetase (mtProRS), respectively. Synthesis of final compounds was achieved through individual reaction steps involving acylation of methyl 3-aminopyrazine-2-carboxylate for preparation of a common intermediate which in turn was used for the...
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Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity I
Brányik, Michal ; Zitko, Jan (advisor) ; Demuth, Jiří (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Title of the thesis: Design, synthesis and evaluation of heterocyclic compounds with potential antimicrobial activity I Author: Michal Brányik Supervisor: doc. PharmDr. Jan Zitko, Ph.D. Consultant: PharmDr. Martin Juhás, Ph.D. Antimicrobial resistance is an ever-growing problem that occurs worldwide. Many bacterial strains develop the ability to resist the otherwise efficient substances, thus posing a serious threat for the future. Mycobacterium tuberculosis (Mtb), the source of tuberculosis, is no exception. Given that it is the leading cause of death due to a single pathogen, many efforts have been put into finding new active compounds. The substances synthesized as a part of this thesis are based on previously prepared substances with potential antimicrobial activity. The basic structure consists of 2-aminooxazole or 2-aminothiazole and substituted pyridine or pyrazine carboxamides. The structures were confirmed by the 1 H and 13 C NMR spectra, IR spectra and mass spectrometry. All the substances were tested for in vitro activity against eight bacterial strains (four gram-positive and four gram-negative) as well as eight fungal strains (four yeast and four fungi). We also...
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Design, synthesis and evaluation of pyridine derivatives as potential antimicrobial compounds
Bachtíková, Andrea ; Zitko, Jan (advisor) ; Demuth, Jiří (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Thesis title: Design, synthesis and evaluation of pyridine derivatives as potential antimicrobial compounds Author: Andrea Bachtíková Thesis supervisor: doc. PharmDr. Jan Zitko, Ph.D. Consultant: PharmDr. Martin Juhás Tuberculosis is a global problem even today. It is the second most common cause of death from infectious diseases according to the WHO and resistance to common antituberculosis drugs, which have been used in therapy for decades, increases. These facts are the main reasons why research into new potential drugs is needed. This thesis presents design, synthesis and evaluation of antimicrobial properties of a series of substituted N-oxazolyl and N-thiazolyl carboxamides of different pyridinecarboxylic acids. Final compounds were characterized by 1 H and 13 C-NMR spectroscopy, IR spectra, melting point and HRMS (High resolution mass spectrometry). Obtained compounds were tested for in vitro activity against M. tuberculosis H37Rv, M. tuberculosis H37Ra and four other clinically less important mycobacterial strains. In addition, compounds were tested for antibacterial activity against four G+ and four G- bacterial strains, antifungal activity against yeasts and fungi,...
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Synthesis and evaluation of N-pyridylbenzamides as potential antimicrobial compounds
Suchánková, Eliška ; Zitko, Jan (advisor) ; Nováková, Veronika (referee)
SYNTHESIS AND EVALUATION OF N-PYRIDYLBENZAMIDES AS POTENTIAL ANTIMICROBIAL COMPOUNDS Eliška Suchánková Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic The derivatives of N-pyridylbenzamide were designed and synthesized to be in vitro tested for antimycobacterial activity against Mycobacterium tuberculosis H37Ra, M. smegmatis, M. aurum and in vitro cytotoxicity in HepG2 cells. These compounds are pyridinyl analogues of previously prepared N-pyrazinylbenzamides that have shown a significant in vitro antimycobacterial activity. The title compounds were synthesized by acylation of aminopyridine or chloropyridine-2-amine by selected benzoyl chlorides. Final compounds were described by elementary analysis, melting point, 1 H and 13 C spectra and IR spectroscopy. Generally, prepared compounds possess lower antimycobacterial activity than previously tested N-pyrazinylbenzamides. However, there are some cases, in which the derivatives of pyridine were more effective compared to the derivatives of pyrazine; mainly against M. smegmatis. The best antimycobacterial activity was proved for derivatives of 2-amino-6-chloropyridine and substituted benzoyl chloride, corresponding with higher lipophilicity of these compounds;...
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Design, synthesis and evaluation of pyrazinamide derivatives as potential antimicrobial compounds II
Kučerová, Lucie ; Zitko, Jan (advisor) ; Miletín, Miroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Lucie Kučerová Supervisor: doc. PharmDr. Jan Zitko, Ph.D. Consultant: PharmDr. Martin Juhás Title of diploma thesis: Design, synthesis and evaluation of pyrazinamide derivatives as potential antimicrobial compounds II Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis complex and is currently one of the most common causes of death from an infectious disease. Treatment of tuberculosis is long-term, combined and controlled to prevent resistance. Resistance is very serious and therefore treatment is always performed with more antituberculars at the same time. Finding new drugs and improving existing ones is a constant part of research. In the theoretical part I tried to summarize information about tuberculosis, its causative agent, diagnostics, possible prevention and treatment strategy. I have described the most commonly used antituberculars, especially the first- line antituberculars - pyrazinamide, from which the derivatives synthesized in my work are based. In the experimental part I described the procedures and reactions used for synthesis of the new compounds, which were formed by combining pyrazinamide with various amino acids. In this...
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Pyrazinamide derivatives as potential antimicrobial compounds
Čečetková, Martina ; Zitko, Jan (advisor) ; Kučerová, Marta (referee)
Charles University, Pharmaceutical Faculty in Hradec Králové Department: Department of Pharmaceutical Chemistry and Pharmaceutical analysis Candidate: Martina Čečetková Supervisor: PharmDr. Jan Zitko, Ph.D. Title of Diploma Thesis: Pyrazinamide derivatives as potential antimicrobial compounds Even in 21st century, tuberculosis still remains a serious and global health threat. Tuberculosis is one of the 10 most common causes of death, the most burdened are developing countries, but this disease infects up to 1/3 of population worldwide. Due to ineffective treatment of tuberculosis in developing countries, the prevalence of tuberculosis which does not respond to standard treatment is increasing. It is necessary to develop new drugs effective against multidrug-resistant tuberculosis and prevent further spread of the disease. The design of final structures is based on previously synthesized molecule 6- chloro-N-(4-(4-fluorophenyl)thiazol-2-yl)pyrazine-2-carboxamide, which structure comes from first line antitubercular pyrazinamide (PZA) and 4-arylthiazol-2-amine scaffold with formerly identified antimycobacterial activity. This starting compound exhibits high activity against M. tuberculosis described by MIC = 0,78 µg/mL and low cytotoxicity. The object of study was to determine effect of substitution...
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Creation and analysis of in-house database of pyrazine derivatives with potential antimicrobial activity
Kebakuile, Legae Gomolemo Boemo ; Zitko, Jan (advisor) ; Kučerová, Marta (referee)
In the early phases of drug design and development, scientists must overcome many challenges involved in identifying potential drug-like or lead-like compounds. This has led to the need of creating large sets of chemical data which will aid in improving the identification of pharmacophores and active compounds. Various scientific fields especially pharmacology, medicinal chemistry and biochemistry have begun to employ the use of computer sciences to aid in the screening for potential leads with more specificity with regards to drug-like compounds' or substances' bioactivity. The emphasis of this project was to create a database containing a collection of pyrazine compounds synthesized overtime in the Faculty of Pharmacy (Charles University, Hradec Kralove) with the aim of having anti-mycobacterium (and possible antibacterial and antifungal) activity, and further utilize this database to predict certain pharmacokinetic and bioavailability properties. This project seeks to demonstrate how certain molecular descriptors can be used as reliable chemoinformation to determine the likeliness or possibility of developing a lead-like or drug-like compound by utilizing computer software. An in-house database of 623 compounds saved in SMILES format was created and used in demonstrating quantitative...
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